Papaya product and calcium chloride emerge as rivals to zinc sterilants

From ANIMAL PEOPLE, September 2010:
(published October 5, 2010)
SAN FRANCISCO, PORTLAND– Contrary to military chow line
rumors circulating for at least seven centuries, saltpeter is just a
meat preservative, with no actual effect in reducing the sex drive
or effecting contraception when troops go on leave. Also contrary to
ancient rumor, troops are not innoculated with saltpeter during
their vaccinations at induction into military service.
Several zinc compounds have contraceptive effects similar to
some of those misattributed to saltpeter if injected into the
testicles of male animals, but often induce painful scrotal
swelling, and have no more effect than saltpeter in reducing
testosterone production.

The latest contenders in the market for male chemosterilants
that will suppress testosterone and will not produce painful side
effects are products based on papaya juice and road salt.
“There seems to be no end of things can can be injected into
testicles to inhibit fertility,” Alliance for Contraception in Cats
& Dogs president Joyce Briggs told ANIMAL PEOPLE. ACC&D
administrates grants to fund demonstrations of EsterilSol,
manufactured and distributed in Mexico by Ark Sciences. Based on
zinc gluconate, EsterilSol is “the same compound” as Neutersol,
according to ACC&D. Introduced in the U.S. in 2003, after a
decade-plus of experimental use in Mexico, Neutersol generated a
brief flurry of enthusiasm worldwide, but was not a commercial
success anywhere. Neutersol produced testicular swelling that the
Blue Cross of India judged unacceptable in a 2005 field test in
Chennai, India, and is no longer made.
Talsur, the first zinc-based chemo-sterilant, developed by
the Blue Cross of India, failed Chennai field tests in 1990-1991.
Talsur was based on zinc arginine.
The newest zinc-based chemosterilant, Infertile, includes
both zinc gluconate and zinc arginine. “Infertile was approved for
use in Brazil in late 2008,” development funder Debbie Hirst told
ANIMAL PEOPLE, “and is now marketed by a firm called Rhobifarma.”
“Studies show that the product provides permanent
sterilization to 72% of dogs in one treatment,” summarizes the ACC&D
evaluation of Infertile. “With further study, and possible
refinement of formulation, Infertile has potential to aid in
advancing sterilization programs in Brazil.”
Zinc injections do not reduce the recipient animals’
production of testosterone. Thus undesirable behavior such as
aggression and territorial marking may not be reduced, or at least
may not be reduced as much, as fast, as by surgical castration.

The papaya fix

Infertile has a Brazilian competitor, StopSex, in
development since 1999 by veterinary researchers Marcelo Vivaqua,
Carmo Fausto Moreira da Silva, and Felipe Berbari Neto, which was
initially introduced specifically to reduce testosterone release from
the testicles of pigs. The active ingredient is papain, extracted
from papaya pulp, in a milk-like solution of lactic acid and glucose.
StopSex “has the fibrosing effect,” explains the product
literature. The lactic acid induces inflammation. The damaged
tissue is replaced by fibrous tissue, while the papain, a substance
best known as a meat tenderizer, “promotes the digestion of
testicular tissue.”
Vivaqua, da Silva, and Neto introduced StopSex as a method
of chemically castrating pigs before slaughter. This is required by
Brazilian law, and by the laws of several other nations, to prevent
“boar taint” from contaminating pork products. StopSex is advertises
as significantly less painful than the conventional procedure of
mechanically castrating pigs without the use of anesthetic.
The idea that StopSex could be adapted for use in
contracepting dogs was raised by Brazilian veterinarian Silvio Leite
during a September 2010 United Nations Food & Agricultural
Organization consultation. Leite opined that unlike hormonal
contraceptive methods, “This product would not be risky in case of
dog meat consumption,” then added that he had no relationship with
the StopSex developers and manufacturers. “Also, I personally do
not endorse dog meat consumption,” Leite said.
Commented Hirst, “We have studied the process of getting a
chemical sterilant approved for use in pigs in Brazil. The economic
and humanitarian justifications are compelling.” But Hirst concluded
that Infertile could not serve the need.
“There is a product that results in the reduction of
andrestenone,” the hormone causing boar taint, “called Vivax,
produced by Pfizer,” Hirst said, “that is a hormone-based
injection which needs to be given twice during the life of the pig,
and then you don’t need to castrate. It took them years to get it
approved at huge expense.”

Road salt

Elaine Lissner, director of medical research programs for
the San Francisco-based Parsemus Foundation, in June 2010 surveyed
ANIMAL PEOPLE readers about perceptions of the importance of altering
the behavior of male animals as a part of sterilization.
“What I’m hearing from the front lines,” Lissner summarized
after the results were in, “is that if you don’t reduce roaming,
packing, fighting, and associated dog bites, there’s not much
point in sterilizing males. The survey response was clear. Most
people thought they could get 30-40% more dog owners through the door
with a non-behavior-changing injection like Neutersol, but for
every-day shelter and street dog use, and for all cats (whether
owned or feral), behavior change is key. Some of the groups using
Neutersol are getting the complication rates down to 1% or 2%, but
neuter/return is more acceptable to the public if the amount of
mating, packing, and fighting goes down.”
Lissner has become intensely interested in the results from
laboratory tests of calcium chloride as an injectible chemosterilant,
done in Kolkata, India, circa 2000.
Calcium chloride is best known as the scale that often builds
up inside tea kettles in areas with “hard” water, and as the form of
salt spread on roads in winter to prevent ice from building up on the
pavement.
Based on the test results, Lissner believes the calcium
chloride approach “reduces testosterone and has a lower complication
rate” than zinc-based solutions. “Also,” Lissner adds, “10%
calcium chloride solution is already widely available in human
emergency rooms. Using the commercially available vials, one could
sterilize a dog right now for under $1.00, or 50 rupees, plus the
cost of a needle. The researchers added a little anesthetic to the
mix, which they think helps keep down swelling.
“Someone just needs to spend the money to take calcium
chloride through the regulatory approvals testing process, which
will cost four to five million dollars,” Lissner told ANIMAL PEOPLE.
“That amount would be saved every month that an injection
substitutes for surgery in the future in the U.S. alone,” Lissner
calculated, “so from a spay/neuter funder’s standpoint, investing
in calcium chloride should be a very good investment in future
savings, and being able to reach more dogs.
Because calcium chloride is a commonly occuring natural
chemical, already in widespread pharmaceutical use, it does not
have economic potential likely to attract for-profit investment.
“My focus,” Lissner said, “has been on making the bigger
funders aware of the amount of published data and trying to get them
interested in partnering with us on taking this through Federal Drug
Administration approval studies. The Parsemus Foundation is too
small to do it ourselves.”
“Our advisor historian Wolfgang Jochle notes that shepherds
in Europe have used calcium chloride for livestock castrations for
many decades,” commented Briggs. “And from discussion with Min
Wang, lead scientist for Neutersol/EsterilSol, it sounds like one
reason they chose zinc gluconate neutralized with arginine as a lead
formula to commercialize was because it worked more quickly than
calcium chloride.”
The difference in time taken to prevent sperm production,
however, if it exists, would be slight compared to the total
reproductive life of a male street dog.